Gunther Felmerer1, Aikaterini Stylianaki1, Rene Hägerling2, Anna Wang3, Philipp Ströbel4, Maija Hollmén5, Nicole Lindenblatt3, Epameinondas Gousopoulos6. 1. Division of Plastic Surgery, Department of Trauma Surgery, Orthopaedics and Plastic Surgery, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany. 2. Molecular and Clinical Sciences Institute, St. George's University of London, London, United Kingdom; Institute of Medical and Human Genetics, Charité Universitätsmedizin Berlin, Berlin, Germany. 3. Clinic of Plastic and Hand Surgery, University Hospital Zurich, Zurich, Switzerland. 4. Institute of Pathology, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany. 5. MediCity Research Laboratory and Institute of Biomedicine, University of Turku, Turku, Finland. 6. Division of Plastic Surgery, Department of Trauma Surgery, Orthopaedics and Plastic Surgery, University Medical Center Göttingen, Georg-August-University, Göttingen, Germany; Clinic of Plastic and Hand Surgery, University Hospital Zurich, Zurich, Switzerland. Electronic address: epameinondas.gousopoulos@usz.ch.
Abstract
BACKGROUND: Lipedema is a common adipose tissue disorder affecting women, characterized by a symmetric subcutaneous adipose tissue deposition, particularly of the lower extremities. Lipedema is usually underdiagnosed, thus remaining an undertreated disease. Importantly, no histopathologic or molecular hallmarks exist to clearly diagnose the disease, which is often misinterpreted as obesity or lymphedema. MATERIALS AND METHODS: The aim of the present study is to characterize in detail morphologic and molecular alterations in the adipose tissue composition of lipedema patients compared with healthy controls. Detailed histopathologic and molecular characterization was performed using lipid and cytokine quantification as well as gene expression arrays. The analysis was conducted on anatomically matched skin and fat tissue biopsies as well as fasting serum probes obtained from 10 lipedema and 11 gender and body mass index-matched control patients. RESULTS: Histologic evaluation of the adipose tissue showed increased intercellular fibrosis and adipocyte hypertrophy. Serum analysis showed an aberrant lipid metabolism without changes in the circulating adipokines. In an adipogenesis gene array, a distinct gene expression profile associated with macrophages was observed. Histologic assessment of the immune cell infiltrate confirmed the increased presence of macrophages, without changes in the T-cell compartment. CONCLUSIONS: Lipedema presents a distinguishable disease with typical tissue architecture and aberrant lipid metabolism, different to obesity or lymphedema. The differentially expressed genes and immune cell infiltration profile in lipedema patients further support these findings.
BACKGROUND:Lipedema is a common adipose tissue disorder affecting women, characterized by a symmetric subcutaneous adipose tissue deposition, particularly of the lower extremities. Lipedema is usually underdiagnosed, thus remaining an undertreated disease. Importantly, no histopathologic or molecular hallmarks exist to clearly diagnose the disease, which is often misinterpreted as obesity or lymphedema. MATERIALS AND METHODS: The aim of the present study is to characterize in detail morphologic and molecular alterations in the adipose tissue composition of lipedemapatients compared with healthy controls. Detailed histopathologic and molecular characterization was performed using lipid and cytokine quantification as well as gene expression arrays. The analysis was conducted on anatomically matched skin and fat tissue biopsies as well as fasting serum probes obtained from 10 lipedema and 11 gender and body mass index-matched control patients. RESULTS: Histologic evaluation of the adipose tissue showed increased intercellular fibrosis and adipocyte hypertrophy. Serum analysis showed an aberrant lipid metabolism without changes in the circulating adipokines. In an adipogenesis gene array, a distinct gene expression profile associated with macrophages was observed. Histologic assessment of the immune cell infiltrate confirmed the increased presence of macrophages, without changes in the T-cell compartment. CONCLUSIONS:Lipedema presents a distinguishable disease with typical tissue architecture and aberrant lipid metabolism, different to obesity or lymphedema. The differentially expressed genes and immune cell infiltration profile in lipedemapatients further support these findings.
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